Yaping Hu

The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines

Please cite this paper as: The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines. Experimental Dermatology 2010; 19: 865–872.

Immuno-histochemical evaluation of solar lentigines: The association of KGF/KGFR and other factors with lesion development

BACKGROUND Solar lentigines (SLs) are macular hyperpigmented lesions associated with sun exposure and age. Histopathologically, SLs are defined by a hyperpigmented basal layer and elongated rete ridges. The molecular mechanisms involved in the formation and the development of SLs are not completely understood. Our earlier data show that keratinocyte growth factor (KGF) induces hyperpigmentary lesions with histological resemblance to SLs. OBJECTIVE To investigate the association of KGF/KGF receptor (KGFR) and other pigmentary genes with the progression of SL development. To better understand the possible role of KGF in the pathology of SLs. METHODS Archived human skin biopsies (24 SLs and 14 healthy skins) were studied using immunohistochemistry for KGF/KGFR, proliferation marker Ki67, stem cell marker keratin-15 (K15), tyrosinase (TYR), stem cell factor (SCF), and protease-activated receptor-2 (PAR-2). RESULTS An increase in TYR-positive cells and expression was found throughout SL progression, as compared to normal skin. The levels of KGF, KGFR, SCF, Ki67 and PAR-2 varied during SL progression. Ki67, K15 and KGF/KGFR were significantly upregulated at early-mid SL stages. The latest-stage SLs expressed the lowest levels of KGF, KGFR, SCF, Ki67 and PAR-2. CONCLUSIONS The upregulation of KGF/KGFR might induce the formation of rete ridges and hyperpigmentation. The reduced levels of all examined proteins (except TYR and K15) suggest a possible inactive status (dormancy or quiescence) of advanced lesions.

Differential levels of elastin fibers and TGF-β signaling in the skin of Caucasians and African Americans.

BACKGROUND While skin color is the most notable difference among ethnic skins the current knowledge on skin physiological and aging properties are based mainly on Caucasian skin studies. OBJECTIVE To evaluate histological differences in elastin fiber network and differential responsiveness to TGF-β in skin of Caucasians and African Americans. METHODS These studies were undertaken using human skin biopsies, primary dermal fibroblasts, Western blot analyses, immunofluorescence microscopy, cDNA array and quantitative real-time PCR. RESULTS In Caucasian subjects, tropoelastin expression and elastin fibers in photoprotected skin was substantially less than in age-matched African American skin. Expression of tropoelastin in photoexposed skin of African American was similar to their photoprotected skin, suggesting that photoexposure did not affect elastin fibers in African American skin to the same extent as Caucasian skin. An elevated level of TGF-β1 present in media from dermal fibroblasts derived from African American skins correlated well with the higher levels of TGF-β mRNA in African American skins analyzed by cDNA array. Treatment with TGF-β1 resulted in a considerably higher induction of elastin mRNA in dermal fibroblasts from African Americans than from Caucasian fibroblasts, indicative of enhanced TGF-β signaling in African American skins. Furthermore, UVA exposure decreased levels of elastin mRNA in Caucasian fibroblasts compared to African Americans fibroblasts. CONCLUSION These results suggest that there are ethnic differences in the elastin fiber network and in TGF-β signaling in African American and Caucasian skin, and that African American have less UV dependent loss of elastin than Caucasian which may contribute to the different perceived aging phenotypes.

Galvanic zinc–copper microparticles inhibit melanogenesis via multiple pigmentary pathways

The endogenous electrical field of human skin plays an important role in many skin functions. However, the biological effects and mechanism of action of externally applied electrical stimulation on skin remain unclear. Recent study showed that galvanic zinc–copper microparticles produce electrical stimulation and reduce inflammatory and immune responses in intact skin, suggesting the important role of electrical stimulation in non-wounded skin. The objective of this study is to investigate the biological effect of galvanic zinc–copper microparticles on skin pigmentation. Our findings showed that galvanic zinc–copper microparticles inhibited melanogenesis in a human melanoma cell line (MNT-1), human keratinocytes and melanoma cells co-cultures, and in pigmented epidermal equivalents. Treatment of galvanic zinc–copper microparticles inhibited melanogenesis by reducing the promoter transactivation of tyrosinase and tyrosinase-related protein-1 in human melanoma cells. In a co-culture Transwell system of keratinocytes and melanoma cells, galvanic zinc–copper microparticles reduced melanin production via downregulation of endothelin-1 secretion from keratinocytes and reduced tyrosinase gene expression in melanoma cells. In addition, exposure of pigmented epidermal equivalents to galvanic zinc–copper microparticles resulted in reduced melanin deposition. In conclusion, our data demonstrated for the first time that galvanic zinc–copper microparticles reduced melanogenesis in melanoma cells and melanin deposition in pigmented epidermal equivalents by affecting multiple pigmentary pathways.